Abstract

PIP: Recognition of a relationship between elevated levels of prostaglandins (PG) and dysmenorrhea represented a major advance. The PGs of most importance in primary dysmenorrhea are assumed to be PGF2alpha and PGE2. Oral contraceptives (OCs), which disrupt the normal sequence of hormonal dominance in the endometrium and reduce menstrual PG production, were the therapeutic agent for dysmenorrhea until the introduction of nonsteroidan antiinflammatory drugs (NSAIDs) with PG synthetase in the mid-1970s. 4 groups of NSAIDs have been evaluated: 1) indomethacin, 2) the fenamates, 3) the arylpropionic acids, and 4) aspirin. Ibuprofen and naproxen, 2 arylpropionic acids, are commonly used to treat dysmenorrhea and have fewer side effects than the other agents. The clinical effectiveness of NSAIDs is ascribed to their inhibition of PG synthestase activity; however, little is known about the pharmacology of these drugs. Reduction of menstrual PG release by ibuprofen or naproxen sodium was shown to produce good to excellent relief in 80% of treatment cycles in a clinical trial, in contrast to placebo therapy which afforded little or no relief. Moreover, in individual subjects there was a positive correlation between the severity of dysmenorrhea and levels of menstrual PG released during the corresponding period. A causal relationship between uterine contractions and dysmenorrheic pain has been demonstrated by other investigators. A current shortcoming of NSAIDs is their lack of specificity. They are assumed to be nonselective agents, affecting PG synthesis in all body tissues and inhibiting PG synthesis indiscriminately. Future research efforts should be directed toward development of a more uterine-selective agent that would produce fewer side effects.